HUMAN 3P RECESSIVE ONCOGENES

人类 3P 隐性癌基因

• 批准号: 2733257
• 负责人: JOHN D. MINNA
• 金额: $ 33.84万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-13 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733257
• 关键词: DNA directed DNA polymerase; DNA footprinting; apoptosis; athymic mouse; autosomal recessive trait; cell growth regulation; enzyme activity; gene deletion mutation; gene expression; human genetic material tag; human tissue; lung neoplasms; molecular cloning; molecular pathology; neoplasm /cancer genetics; northern blottings; nucleic acid sequence; oncogenes; polymerase chain reaction; protein sequence; pulsed field gel electrophoresis; single strand conformation polymorphism; southern blotting; statistics /biometry; telomerase; telomere; tissue /cell culture

DESCRIPTION (Adapted from the Investigator's Abstract): This is a new proposal to identify and study the function of a putative recessive tumor suppressor gene or genes in 3p21.3 important in the development of lung cancers. Evidence for such a tumor suppressor comes from studies showing the early loss of 3p21 alleles in preneoplasia, and allele loss of 3p genes in 70-80% of both small cell and non-small cell lung cancers. In specific aim I it is proposed to clone the gene using a series of resources including a set of homozygous deletions in lung tumor cell lines defining a 350 kb and potentially 30 kb critical region, and a high resolution physical and transcription map with 25 cDNA clones already identified in this region. Specific aim 2 is to determine functional characteristics of this locus by introduction of portions of chromosome 3p into human lung cancer lines bearing a 3p21.3 abnormality, and testing for suppression of tumorigenicity using nude mice, soft agarose culture and studies of apoptosis. In specific aim 3 the applicant plans to follow up on an observation that this region might be involved in suppressing telomerase activity by investigating telomere length and telomerase function in lung cancer cells altered by gene transfer.

描述（改编自研究者摘要）：这是一个新的 识别和研究假定隐性肿瘤功能的提案 3p21.3 中的一个或多个抑制基因对肺发育很重要 癌症。 这种肿瘤抑制剂的证据来自研究表明 肿瘤前期 3p21 等位基因的早期丢失以及 3p 基因的等位基因丢失 70-80% 的小细胞和非小细胞肺癌。 具体来说 目标 I 建议使用一系列资源克隆该基因，包括 肺肿瘤细胞系中的一组纯合缺失，定义了 350 kb 和 潜在的 30 kb 关键区域，以及高分辨率物理和 转录图谱包含该区域已鉴定的 25 个 cDNA 克隆。 具体目标 2 是通过以下方式确定该基因座的功能特征： 将 3p 染色体部分引入人类肺癌细胞系 具有 3p21.3 异常，并测试抑制致瘤性 采用裸鼠、软琼脂糖培养和细胞凋亡研究。 具体来说 目标 3 申请人计划对该地区的观察结果进行跟进 通过调查可能参与抑制端粒酶活性 基因改变肺癌细胞的端粒长度和端粒酶功能 转移。